Restless legs syndrome in end-stage renal disease: Clinical characteristics and associated comorbidities

BackgroundDespite being frequently described in patients with end-stage renal disease (ESRD), clinical characteristics and comorbidities in association with restless legs syndrome (RLS) are still to be confirmed.ObjectivesThe aim of this study was to investigate clinical factors associated with RLS in ESRD patients in hemodialysis.MethodsThis is a cross-sectional study of 400 patients on hemodialysis, evaluating RLS, clinical features and other sleep abnormalities.ResultsOut of 400, 86 patients presented RLS (21.5%; mean age 48.8 ± 13.8 y), being more frequent in females (p < 0.005). Forty-eight individuals (12% mean age 50.7 ± 13.1 y) had moderate/severe RLS, 14 reported symptoms prior to hemodialysis, 13 described family history of RLS, and eight described symptoms as disturbing during dialysis. RLS cases showed lower hemoglobin (p < 0.005), poorer quality of sleep (Pittsburgh Sleep Quality Index >5, p = 0.002), higher scores on the Beck Depression Inventory Scale (p < 0.005), greater scores on the Charlson Comorbidity Index (p = 0.01) and the Epworth Sleepiness Scale (p = 0.001) and higher risk of obstructive sleep apnea (OSA; Berlin questionnaire, p = 0.01). Hypertension was more frequent in cases with moderate/severe RLS (p = 0.01) and remained after controlling for the risk of OSA (p = 0.02).ConclusionIn ESRD patients in hemodialysis, RLS is present in 21.5%; 16% report symptoms prior to hemodialysis and a family history of RLS. Symptoms are disturbing during hemodialysis in 9% of cases. RLS is associated with lower hemoglobin, worse sleep quality, excessive daytime sleepiness, depressive symptoms and higher risk of OSA. Hypertension is associated with moderate/severe RLS.     

Assessing health-related quality of life in patients with restless legs syndrome in Korea: Comparison with other chronic medical diseases

BackgroundThere have been few quality of life (QoL) studies of patients with restless legs syndrome (RLS) in Asian countries. We studied the QoL of patients with RLS and compared it to normal controls and patients with hypertension, type 2 diabetes, or osteoarthritis in Korea.MethodsA total of 215 RLS patients (141 female; mean age 51.7 ± 13.5) were enrolled. All patients completed the questionnaires, including all the Korean versions of SF-36, RLS QoL, the International RLS Severity scale (IRLS), the Pittsburgh Sleep Quality Index (PSQI), and the Beck Depression Inventory-2 (BDI-2). These results were compared with the scores from normal controls (N = 214) and from patients with hypertension (196), uncomplicated type 2 diabetes (185), or osteoarthritis of the knee (177).ResultsThe SF-36 QoL in patients with RLS was lower than that of the normal controls, and even lower than patients with hypertension or diabetes, but higher than those with osteoarthritis. The SF-36 Qol of RLS patients showed a significantly negative correlation with the severity of RLS symptoms (r = ?0.430, p < 0.001) and the severity of depression (r = ?0.565, p < 0.001), but was not significantly related to gender, age, or age-of-symptom onset (early or late-onset). Step-wise multiple regression identified three factors related to SF-36 QoL: depression (46.5% of RLS had responses on BDI-2 indicating depression) (β = ?.899, p < 0.001), RLS symptom severity (K-IRLS) (β = ?.718, p < 0.001), and gender (female) (β = ?6.128, p = 0.007).ConclusionsThese findings show that RLS has a considerable impact on the QoL of Koreans, which is comparable with studies of western countries. The QoL impairment relates to the degree of depression with RLS for Koreans.     

Elevated C-reactive protein is associated with severe periodic leg movements of sleep in patients with restless legs syndrome

BackgroundRestless legs syndrome (RLS) is a common sleep disorder in which urges to move the legs are felt during rest, are felt at night, and are improved by leg movement. RLS has been implicated in the development of cardiovascular disease. Periodic leg movements (PLMs) may be a mediator of this relationship. We evaluated systemic inflammation and PLMs in RLS patients to further assess cardiovascular risk.Methods137 RLS patients had PLM measurements taken while unmedicated for RLS. Banked plasma was assayed for high sensitivity C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha).ResultsMean (SD) PLM index was 19.3 (22.0). PLMs were unrelated to TNF-a and IL-6, but were modestly correlated with log CRP (r(129) = 0.19, p = 0.03). Those patients with at least 45 PLMs/h had an odds ratio of 3.56 (95% CI 1.26–10.03, p = 0.02, df = 1) for having elevated CRP compared to those with fewer than 45 PLMs/h. After adjustment for age, race, gender, diabetes, hypertension, hyperlipidemia, inflammatory disorders, CRP-lowering medications, and body mass index, the OR for those with ?45 PLMs/h was 8.60 (95% CI 1.23 to 60.17, p = 0.03, df = 10).ConclusionsPLMs are associated with increased inflammation, such that those RLS patients with at least 45 PLMs/h had more than triple the odds of elevated CRP than those with fewer PLMs. Further investigation into PLMs and inflammation is warranted.     

Efficacy and safety of pramipexole in Japanese patients with primary restless legs syndrome: A polysomnographic randomized,double-blind,placebo-controlled study

ObjectiveTo evaluate the efficacy of pramipexole on polysomnographic measures, patient ratings and a clinical rating in Japanese patients with primary restless legs syndrome (RLS).MethodsPatients with moderate to severe RLS having periodic limb movements in bed index (PLMI) ? 5 were randomly assigned to receive pramipexole or placebo in a 6-week, double-blind, placebo-controlled study with forced titration from 0.125 to 0.75 mg/day. Both polysomnography (PSG) and the suggested immobilization test (SIT) were performed at baseline and 6 weeks after starting treatment.ResultsThe analysis of covariance of log-transformed PLMI showed that the adjusted means at the end of study were significantly smaller in the pramipexole group than in the placebo group (p = 0.0019). In all patients, variables on SIT did not show any differences between the two groups, whereas a significant improvement was shown in the pramipexole group compared with the placebo group for patients with a SIT-PLM index at baseline ? 15. Pramipexole group showed a significant reduction in the International Restless Legs Syndrome Study Group rating scale (IRLS; p = 0.0005), a significant improvement in both Patient Global Impression (PGI; p < 0.0001) and Clinical Global Impressions (CGI-I; p = 0.0488), and a significantly greater mean reduction in the Pittsburgh Sleep Quality Index (PSQI; p = 0.0016), when compared with those of placebo group at week 6.ConclusionsPramipexole is highly efficacious in the reduction of PLMI and in the improvement of subjective severity of RLS and subjective sleep disturbance caused by the disorder.     

Subcortical structural abnormalities in juvenile myoclonic epilepsy (JME): MR volumetry and vertex based analysis

PurposeImaging studies in juvenile myoclonic epilepsy (JME) have shown abnormalities of the thalamus and frontal cortex. The purpose of this study was to systematically investigate the morphological changes in the deep gray matter (GM) structures using techniques of voxel based morphometry (VBM), MR volumetry and shape analysis.MethodologyThe study included 40 patients with JME (M:F = 21:19; age 22.8 ± 5.3 years) and 19 matched controls (M:F = 13:6; age 24.5 ± 4.2 years). All subjects underwent MRI using standard protocol that included T1-3D TFE (Turbo Field Echo) images with 1 mm thickness. VBM analysis and MR volumetry were performed. The volumes of deep subcortical GM structures were extracted and vertex-wise shape analysis was performed using FSL-FIRST (FSL-Integrated Registration and Segmentation Toolbox) software.ResultsVBM analysis with a thalamic mask revealed focal thalamic alterations in the anteromedial aspect of the thalamus (p < 0.05, false discovery rate (FDR) corrected) which remained significant after adjusting for age, gender and intracranial volume (ICV). Significant volume loss was noted in both the thalami. Vertex-wise shape analysis showed significant focal surface reductions in the thalami bilaterally in patients that were predominantly seen in the medial as well as lateral aspects of the thalamus (p < 0.05, FDR corrected). The disease duration correlated with left hippocampus volume while age of onset correlated with right hippocampus volume.ConclusionsThis study confirms the presence of thalamic alterations in patients with JME. Shape analysis technique provided complementary information and disclosed the presence of focal atrophic changes in patients’ thalami. The striatum and hippocampus did not show any significant alterations.     

Increased prevalence of nocturnal smoking in restless legs syndrome (RLS)

ObjectiveWe investigated the prevalence of nocturnal smoking (NS) in patients with RLS.MethodsOne hundred RLS patients living in Emilia-Romagna (Northern Italy) and 100 matched controls, randomly selected from the general population, underwent interviews for the presence of nocturnal smoking and for obsessive-compulsive traits, depression, excessive daytime sleepiness (EDS) and subjective sleep quality.ResultsNS was more prevalent in RLS patients than controls (lifetime prevalence: 12% vs. 2%, P = 0.012). Patients with NS had more frequently Sleep-Related Eating Disorders (SRED) than patients without NS (83.3% vs. 26.1%, P = 0.0002). Pathological and borderline Maudsley Obsessive-Compulsive Inventory (MOCI) values as well as pathological values at the Beck Depression Inventory (BDI) increased from controls to RLS patients without NS to RLS patients with NS (P = 0.005 and P = 0.01, respectively).ConclusionsWe demonstrate an increased prevalence of NS in patients with RLS, in many cases associated with increased SRED. NS may be associated with psychopathological traits in RLS and may be relevant in the management of RLS patients.     

The severity range of restless legs syndrome (RLS) and augmentation in a prospective patient cohort: Association with ferritin levels

ObjectivesThe aim of the study was to prospectively examine all patients with a diagnosis of RLS consulting a sleep disorders clinic and to assess RLS severity and augmentation and their associations, including ferritin levels.MethodsPatients were stratified into patients with RLS as ancillary diagnosis, RLS sufferers without current augmentation and RLS sufferers with current augmentation. Work-up included RLS severity scales and blood biochemical variables including indices of iron metabolism.ResultsIn an 18-month period, 302 patients with RLS (183 women, 119 men; mean age, 59.1 ± 13.7 years) were recruited. RLS was considered idiopathic in 291 patients (96.4%). Most patients (240, 79.5%) were RLS sufferers, whereas the remaining 62 (20.5%) had RLS as ancillary diagnosis. Nineteen out of 162 patients treated with dopaminergic agents (11.7%) had current augmentation. Almost one-third of all patients (31.1%) had ferritin levels <50 μg/l. Patients with an ancillary diagnosis of RLS had higher ferritin levels than RLS sufferers without current augmentation. The lowest ferritin levels were present in RLS sufferers with current augmentation 132.8 ± 98.0 μg/l vs. 100.6 ± 84.5 μg/l vs. 55.8 ± 43.6 μg/l; p = 0.002). Patients with augmentation did not differ from non-augmented patients regarding age, gender, RLS etiology, presence of previous augmentation, or any other documented comorbidity (p > 0.05).ConclusionThe severity spectrum of RLS in this clinical cohort ranged from the ancillary diagnosis of RLS to augmented RLS. There was an inverse correlation between RLS severity and ferritin levels. Patients with current augmentation had the lowest ferritin levels. Our data further strengthen a putative role of low iron stores as a potential aggravator of idiopathic RLS. Moreover, low ferritin might represent a potential biomarker of RLS augmentation under dopaminergic therapy.     

Nocturnal eating is part of the clinical spectrum of restless legs syndrome and an underestimated risk factor for increased body mass index

ObjectivesWe aimed to investigate the prevalence of night eating syndrome (NES) in a large cohort of patients with restless legs syndrome (RLS).MethodsOur cross-sectional study included 120 patients examined at the University of Bologna Centre for Sleep Disorders, Bologna, Italy, and met all four International RLS criteria for the diagnosis of RLS. Each patient underwent a semistructured telephone interview investigating demographic data and general health status, RLS features and severity, presence of excessive daytime sleepiness, and presence of NES.ResultsThe sample included 37 men and 83 women with a mean age of 63.8 ± 11.5 years. There were 31% of patients who reported episodes of nocturnal eating (NE); among them, 17% fulfilled the new diagnostic criteria for NES. Comparing RLS patients with and without NE, there were no differences in RLS features. However, RLS patients with NE were older (67.2 ± 11.6 vs 62.4 ± 11; P = .038), were in a higher body mass index (BMI) range (27.7 ± 3.8 vs 26.1 ± 4.1 kg/m²; P = .023), were taking more drugs for concomitant diseases (89% vs 72%; P = .031), were more likely to report insomnia (40% vs 23%; P = .041), and were using more hypnotic agents (37.8% vs 19.3%; P = .050) and dopaminergic drugs (65% vs 46%; P = .041). When comparing those RLS patients with NES diagnostic criteria and those without NES, no differences emerged in demographic, clinical, and RLS features; however, NES patients were in a higher BMI range (28.3 ± 4.1 vs 26.2 ± 3.9 kg/m², P = .037), were more frequently smokers (43% vs 17%; P = .027), and were more frequently using hypnotic agents (30% vs 24%; P = .025). Lastly, no differences were found when comparing patients with a NES diagnosis and those with NE not fitting the diagnostic criteria for NES, except for a higher use of benzodiazepine drugs (BDZ) in this latter subgroup (29% vs zero; P = .014).ConclusionsA nocturnal compulsion to eat seems to be an intrinsic part of the clinical spectrum of RLS manifestations and an odd risk factor for increases in BMI in RLS patients. However, it is still not clear if NE in RLS would fit in one of the two known categorized syndromes of NE (i.e., sleep-related eating disorder [SRED] or NES) or if it represents a different strictly RLS-related eating behavior.     

Leptomeningeal failure in patients with breast cancer receiving stereotactic radiosurgery for brain metastases

PurposePrior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS).MethodsBetween 2000–2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54 months (range, 0–106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fisher’s-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models.ResultsOf 149 patients, 21 (14%) developed LMF (median time of 11.9 months). None of the following predicted for LMF: Her2-status (HR = 0.49, p = 0.16), hormone-receptor status (HR = 1.15, p = 0.79), prior craniotomy (HR = 1.58, p = 0.42), prior WBRT (HR = 1.36, p = 0.55). Non-significant factors between patients that did (n = 21) and did not (n = 106) develop LMF included neurologic death (p = 0.34) and median survival (8.6 vs 14.2 months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p = 0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1 months (IQR 3.4–7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1 months) than in other (1.7 months) histologiesConclusionBreast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast patients.     

Reduced gray matter volume in psychotic disorder patients with a history of childhood sexual abuse

Childhood trauma is associated with smaller gray matter volume, similar to the pattern seen in psychotic disorders. We explored the relationship between childhood abuse, psychosis, and brain volume in a group of 60 individuals with a psychotic disorder and 26 healthy control subjects. We used voxel-based morphometry (VBM) to quantify gray and white matter volume and the Childhood Trauma Questionnaire (CTQ) to measure childhood abuse. Within the psychotic disorder group, total gray matter volume was inversely correlated with the severity of childhood sexual abuse (r = ? .34, p = .008), but not the other types of abuse. When the 24 patients with sexual abuse were compared with demographically matched samples of 23 patients without sexual abuse and 26 control subjects, only patients with a history of sexual abuse had reduced total gray matter volume (t(48) = 2.3, p = .03; Cohen's d = .63). Voxel-based analysis revealed a cluster in the prefrontal cortex where volume was negatively correlated with sexual abuse severity. Voxel based comparison of the three matched groups revealed a similar pattern of results, with widespread reductions in psychosis patients with sexual abuse relative to controls that were not found in psychosis patients without sexual abuse. These findings indicate that some of the variance of gray matter volume in psychotic disorders can be explained by a history of sexual abuse.     

Long-term outcome and tolerability of the ketogenic diet in drug-resistant childhood epilepsy—The Austrian experience

PurposeTo evaluate the long-term efficacy/tolerability of the ketogenic diet (KD) in paediatric drug-resistant epilepsies.MethodsData from children who were treated between 1999 and 2008 and had continuous follow-up of at least 6 months after initiation of the KD were analysed retrospectively. Response was defined as ≥50% seizure reduction. Treatment effects on EEG, developmental outcome and the “outcome-predictive” value of various clinical factors were also assessed.Results50 children (22 boys; mean age 4.5 years ± 3.55) were included. Mean follow-up was 3.93 ± 2.95. 50% of the patients were responders, 48% of them became seizure free. 50% were non-responders, 20% of them deteriorated. In responders, EEG background activity improved significantly (p = 0.014) and a significantly lower rate of epileptic discharges (p = 0.009) was seen after 6 months. In addition, neurological examination findings demonstrated significant developmental progress (p = 0.038).Favourable treatment outcome was associated with a shorter disease duration (p = 0.025) and generalised tonic clonic seizures (p = 0.059). No further significant outcome predictors were detected. However, response was 44% in patients with infantile spasms, 62.5% in those with Dravet syndrome and 50% in Lennox-Gastaut-syndrome.Side effects occurred in 28%, but discontinuation of the KD was not required in any case. They most often observed with concomitant topiramate (p = 0.001) and valproate (p = 0.046).ConclusionDespite the retrospective nature of the study and the inhomogeneous patient sample, we found good long-term effects of the KD on seizure frequency, EEG and neurological development.     

Distribution of regional gray matter abnormalities in a pediatric population with temporal lobe epilepsy and correlation with neuropsychological performance

ObjectiveThe goals of the work described here were to determine if hippocampal and extrahippocampal atrophy in children with temporal lobe epilepsy (TLE) follows a pattern similar to that in adult patients, and to assess the clinical and neuropsychological relevance of regional brain atrophy in pediatric TLE.MethodsChildren with symptomatic TLE (n = 14: 9 with mesial TLE due to hippocampal atrophy and 5 with TLE due to neocortical lesions), healthy children (n = 14), and 9 adults with mesial temporal lobe epilepsy (MTLE) were compared using voxel-based morphometry (VBM) of brain magnetic resonance imaging (MRI). The children underwent a comprehensive neuropsychological battery.ResultsChildren with MTLE with unilateral hippocampal atrophy (n = 9) exhibited a significant reduction in gray matter in the hippocampus ipsilateral to the seizure origin and significant atrophy in the ipsilateral cingulate gyrus and contralateral middle frontal lobe. Children with TLE (n = 14) exhibited a significant reduction in the gray matter of the ipsilateral hippocampus and parahippocampal gyrus. There was a correlation between gray matter volume in children with TLE and scores on several neuropsychological tests. Atrophy in pediatric patients with MTLE was less extensive than that in adults, and involved the hippocampi and the frontal cortex.ConclusionsSimilar to adult MTLE, pediatric MTLE is associated with hippocampal and extrahippocampal cell loss. However, children display less intense quantifiable gray matter atrophy, which affects predominantly frontal lobe areas. There was a significant association between volume of gray matter in medial temporal and frontal regions and scores on neuropsychological tests. In childhood, TLE and the concomitant cognitive/behavior disturbances are the result of a damaged neural network.     

Topography of sensory symptoms in patients with drug-naïve restless legs syndrome

ObjectivesWe aimed to describe the sensory topography of restless legs syndrome (RLS) sensory symptoms and to identify the relationship between topography and clinical variables.MethodsEighty adult patients with drug-naïve RLS who had symptoms for more than 1 year were consecutively recruited. During face-to-face interviews using a structured paper and pencil questionnaire with all participants, we obtained clinical information and also marked the topography of RLS sensory symptoms on a specified body template, all of which were subsequently inputted into our in-house software. The RLS sensory topography patterns were classified according to localization, lateralization, and symmetry. We investigated if these sensory topography patterns differed according to various clinical variables.ResultsThe lower extremities only (LE) were the most common location (72.5%), and 76.3% of participants exhibited symmetric sensory topography. Late-onset RLS showed more asymmetric sensory distribution compared with early-onset RLS (P = .024). Patients whose sensory symptoms involved the lower extremities in addition to other body parts (LE-PLUS) showed more severe RLS compared with those involving the LE (P = .037).ConclusionRLS sensory symptoms typically were symmetrically located in the lower extremities. LE-PLUS or an asymmetric distribution more often occurred in patients with more severe RLS symptoms or late-onset RLS.     

Restless legs syndrome, sleep impairment, and fatigue in chronic obstructive pulmonary disease

ObjectiveTo investigate the frequency of factors associated with restless legs syndrome (RLS) in patients with chronic obstructive pulmonary disease (COPD).MethodsRLS diagnosis was investigated (International RLS Study Group, IRLSSG) and severity was assessed (IRLS rating scale) in 104 consecutive COPD patients (age 69.1 ± 8). Other measures were dyspnea severity (Modified Medical Research Council, MMRC), sleep quality (Pittsburgh Sleep Quality Index, PSQI), daytime somnolence (Epworth Sleepiness Scale, ESS), depressive symptoms (Beck Depression Inventory, BDI-II), and fatigue (Fatigue Severity Scale, FSS). Laboratory values included hemoglobin, ferritin, creatinine, and fibrinogen.ResultsThirty-two patients (30.8%) were diagnosed with RLS (65.6% women), which was moderate/severe (IRLS >11) in 26 (81.3%). RLS symptoms started after age 40 in most patients (93.3%). RLS patients had poorer sleep quality (PSQI >5 = 59.6%; p = 0.002), worse fatigue (FSS >27 = 51%; p = 0.005), and more depressive symptoms (BDI-II >10 = 14.4%; p = 0.005). Patients with RLS also presented more severe dyspnea (p = 0.009) and lower creatinine levels (p = 0.005). Overall, fatigue severity was correlated with older age (p = 0.001); level of dyspnea was positively correlated with PSQI and FSS (p < 0.005) and negatively correlated with ferritin (p = 0.03) and creatinine (p = 0.005), and PSQI scores correlated positively with FSS (p < 0.005) and negatively with ferritin (p = 0.005) and creatinine (p = 0.02). Quality of sleep was independently predicted by dyspnea severity and creatinine and fatigue by age and depression.ConclusionRLS is common in COPD. Patients with RLS have low creatinine, poorer quality of sleep, and more fatigue and depressive symptoms. RLS symptom severity is correlated to lower ferritin and severity of dyspnea.     

Prevalence and clinical characteristics of restless legs syndrome in diabetic peripheral neuropathy: comparison with chronic osteoarthritis

BackgroundThe prevalence of restless legs syndrome (RLS) in patients with peripheral neuropathy has been reported to be higher than that of the general population in some studies, which suggests an association between neuropathy and RLS, but not all studies show increased RLS with neuropathy. These differences may reflect adequacy of the diagnosis, effects of chronic pain complicating the diagnosis, or population differences. Moreover, if there is increased risk for RLS with neuropathy, it may reflect consequences of the chronic pain rather than other aspects of diabetes mellitus (DM). Therefore, we investigated the effects of diagnosis rigor on the estimated prevalence of RLS in patients with diabetic peripheral neuropathy (DPN) and those with chronic leg pain from osteoarthritis (OA), and then we compared the RLS prevalence in these two populations with each other and with population prevalence for Korea.MethodsOur study is a prospective case-control study of 199 patients with DPN and 220 patients with OA. After evaluating the presence of RLS in these subjects using the diagnostic criteria of the International RLS Study Group, we confirmed the diagnosis of RLS through face-to-face interviews using the 18-item Hopkins Diagnostic Questionnaire, which removes RLS mimics; and through independent examinations by two neurologists.ResultsOf the 199 subjects with DPN, 44 (22%) appeared to have RLS from their answers on the 4-item RLS diagnostic questionnaire compared to 8 (3.6%) of 220 subjects with OA. However, the prevalence of RLS in the DPN group dropped to 16 (8%) subjects but stayed at 8 (3.6%) OA subjects when using the Hopkins Telephone Diagnostic Interview (HTDI) adapted for clinical interview. The RLS prevalence determined by HTDI remained significantly higher (P = .042) in the DPN group compared to the OA group and was twice that reported for the general Korean population (8% vs 3.9%). Among subjects with DPN, those with RLS were older (68.06 ± 8.43 years vs 62.46 ± 11.05 years; P = .049) and had higher pain scores (visual analog scale [VAS], 4.69 ± 2.52 vs 2.72 ± 2.12; P = .002). The quality of sleep (MOS [Medical Outcomes Study] sleep scale) and health-related quality of life (QoL) (total score on the 36-Item Short-Form Health Survey [SF-36]) showed no significant difference between the two groups.ConclusionsThe prevalence of RLS in patients with DPN cannot be accurately assessed with only the four diagnostic criteria interview, but the prevalence was higher than expected for Koreans from the general population prevalence and also was higher than occurred with OA patients with chronic leg pains when accurately assessed with a structured interview. Chronic leg pain from OA does not significantly complicate RLS diagnosis, and chronic pain itself does not explain the increased RLS prevalence in diabetic neuropathy.     

Is preeclampsia associated with restless legs syndrome?

ObjectiveRestless legs syndrome (RLS) is a common neurologic disorder. Secondary RLS includes pregnancy and iron deficiency. Prevalence of RLS in pregnancy ranges from 11% to 27%. We aimed to assess the frequency and characteristics of RLS in pregnancy in a Peruvian population and to evaluate the possible pregnancy or delivery complications due to RLS.MethodsWe assessed 218 consecutive expectant mothers at the inpatient clinic of the Hospital San Bartolome in Lima, Peru. Assessment was performed by using the standard diagnostic criteria for RLS and by using a clinical and diagnostic interview. Questionnaires for RLS severity, idiopathic RLS (IRLS), and excessive daytime sleepiness (EDS) according to the Epworth sleepiness scale (ESS) were used. Blood examination was performed for hemoglobin and hematocrit. For comparison, RLS patients were matched for age and body mass index (BMI) with pregnant women without RLS.ResultsOut of 218 patients, 40 (18.4%) fulfilled diagnostic criteria for RLS. In RLS patients, prophylactic iron supplementation therapy during pregnancy was less frequently taken (P = .02). Pregnant women with RLS had a higher ESS score than pregnant controls (10.6 +/− 3.1 vs 7.6. +/− 3.6; P < .001). Preeclampsia was more frequent in RLS (7/40 vs 1/39; P = .03).ConclusionsIn our study, RLS was frequent in pregnant Peruvian women, especially in those without prophylactic iron supplementation. RLS patients described more EDS. Preeclampsia was more common in RLS. Our study is the first study to indicate a possible association between RLS and preeclampsia.     

Assessment of nitric oxide, advanced oxidation protein products, malondialdehyde, and thiol levels in patients with restless legs syndrome

ObjectivesWe aimed to determine the importance of oxidative stress in the pathogenesis of restless legs syndrome (RLS) by quantification of advanced oxidation protein products and total thiol levels (as markers of oxidative protein damage), nitric oxide levels (as an antioxidant and endothelial function), and malondialdehyde levels (as a marker of lipid peroxidation) in patients with RLS.Design and methodsA total of 22 patients with primary RLS were enrolled in the study and 20 age-and-gender-matched healthy subjects were enrolled as a control group. Serum nitric oxide, malondialdehyde, thiol levels, and plasma advanced oxidation protein products levels were determined by spectrophotometric methods.ResultsSerum nitric oxide and thiol levels were lower in the patient group than in controls (p = 0.007 and p = 0.017, respectively). Plasma advanced oxidation protein products levels and serum malondialdehyde levels were found to be higher in patients with RLS than in controls (p = 0.017 and p = 0.008, respectively). Serum malondialdehyde level was found to be positively correlated with plasma advanced oxidation protein products levels (p = 0.039). Serum thiol level was found to be negatively correlated with plasma advanced oxidation protein products levels (p = 0.030).ConclusionsIncreased advanced oxidation protein products, malondialdehyde levels, and decreased thiol and nitric oxide levels, may suggest that patients with RLS are under oxidative stress. Although both lipid peroxidation and protein oxidation may have a role in atherosclerosis in RLS, those factors may be related to the pathogenesis of RLS.     

Endoscopic endonasal approach to pituitary adenomas: Impact on adenohypophyseal function. Study of 231 cases

PurposeTo identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs).MethodsRetrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years.Results242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n = 72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR = 3.9, p = 0.046) and operated in the first four years of the neurosurgeon's learning curve (OR = 5.7, p = 0.016) presented a higher risk of developing postoperative hypopituitarism.Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR = 10.5, p = 0.024). Patients with presurgical visual impairment (OR = 30.0, p = 0.010) and PAs >3 cm (OR = 14.0, p = 0.027) had higher risk of developing new pituitary deficits.ConclusionApproximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size >3 cm have a higher risk of postoperative hypopituitarism.     

Is denial a maladaptive coping mechanism which prolongs pre-hospital delay in patients with ST-segment elevation myocardial infarction?

ObjectiveDuring an acute myocardial infarction, patients often use denial as a coping mechanism which may provide positive mood regulating effects but may also prolong prehospital delay time (PHD). However, empirical evidences are still sparse.MethodsThis cross-sectional study included 533 ST-elevated myocardial infarction (STEMI) patients from the Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Data on sociodemographic, clinical and psycho-behavioral characteristics were collected at bedside. The outcome was assessed using the Cardiac Denial of Impact Scale (CDIS) with the median split as cutoff point. A total of 206 (41.8%) STEMI patients were thus classified as deniers.ResultsDeniers were less likely to suffer from major depression (p = 0.04), anxiety (p = 0.01) and suboptimal well-being (p = 0.01) compared to non-deniers during the last six months prior to STEMI. During STEMI, they were less likely to perceive severe pain strength (p = 0.04) and racing heart (p = 0.02). Male deniers were also less likely to perceive shortness of breath (p = 0.03) and vomiting (p = 0.01). Denial was not associated with overall delay time. However, in the time window of 3 to 24 h, denial accounted for roughly 40 min extra delay (356 vs. 316.5 min p = 0.02 n = 196).ConclusionsDenial not only contributes to less suffering from acute heart related symptoms and negative affectivity but also leads to a clinically significant delay in the prevalent group.